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The aim of this study was to investigate the relationship between hepatotoxicity, levels of glucuronide conjugates of valproic acid (VPA), and the toxic metabolites of VPA (4-ene VPA and 2,4-diene VPA). We also examined whether hepatotoxicity could be predicted by the urinary excretion

levels of VPA and its toxic metabolites. VPA was administrated orally in rats in amounts ranging from 20 mg/kg to 500 mg/kg. Free and total (free plus glucuronide conjugated) VPA, 4-ene VPA, and 2,4-diene VPA were quantified in urine and liver using gas chromatography-mass spectrometry. Serum levels of aspartate aminotransferase, alanine aminotransferase, and α-glutathione

S-transferase (α-GST) were also determined to measure the level of hepatotoxicity. The serum α-GST level increased slightly at the 20 mg/kg dose, and substantially increased at the 100 and 500 mg/kg dose; aspartate aminotransferase and alanine aminotransferase levels did not change with the administration of increasing doses of VPA. The liver concentration of free 4-

ene VPA and the urinary excretion of total 4-ene VPA were the only measures that correlated with the increase in the serum α-GST level (p < 0.094 and p < 0.023 respectively). From these results, we conclude that hepatotoxicity of VPA correlates with liver concentration of 4-ene VPA and can be predicted by the urinary excretion of total 4-ene VPA.

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Synthesis and biological evaluations of enoxacin carboxamide derivatives M. Saeed Arayne ;Najma Sultana ;Urooj Haroon ;M. Ahmed Mesaik ;Muhammad Asif pp.967-974

Novel facile synthesis of imidazo[1,2-b]-[1,2,4,5]tetrazines with potential antimicrobial activity Ahmad Sami Shawali ;Nagla M. Tawfik pp.975-982

Anti-lipase and lipolytic activities of ursolic acid isolated from the roots of Actinidia arguta Junghyun Kim ;Dae Sik Jang ;Hyojun Kim ;Jin Sook Kim pp.983-987

Analysis of Fuzhisan and quantitation of baicalin and ginsenoside Rb₁ by HPLC-DAD-ELSD Jingkun Zhao ;Desheng Wang ;Shurong Duan ;Jianxiu Wang ;Jing Bai ;Wenlan Li pp.989-996

Natural anti-inflammatory compounds for the management and adjuvant therapy of inflammatory bowel disease and its drug delivery system Hyun-Jo Kim ;Constantinos Neophytou pp.997-1004

Comparative antihypertensive activities of losartan and HM70186 in rats with hepatic dysfunction Jae-Hong Choi ;Sunhee Shin ;Dongsun Park ;Jeong Hee Jeon ;Bong Ho Choi ;Min-Jung Jang ;Seong Soo Joo pp.1005-1011

Human papollimavirus 16 and 18L1 serology in Korean women with high-grade cervical intraepithelial neoplasia and cervical cancer Nan-Hee Jeong ;Mi-Kyung Woo ;Nak-Woo Lee ;Sook-Jin Hur ;Kum-Sook Choi ;Hong-Jin Kim pp.1013-1018

Micrometritics and release behaviours of cellulose acetate butyrate microspheres containing theophylline prepared by emulsion solvent evaporation and emulsion non-solvent addition method Mitra Jelvehgari ;Fatemeh Atapour ;Ali Nokhodchi pp.1019-1028

The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid Min Sun Lee ;Young-Joo Lee ;Bo Joon Kim ;Kye Jung Shin ;Bong Chul Chung ;Du-Jong Baek ;Byung Hwa Jun pp.1029-1035

Protective effects of caspase-9 and poly(ADP-ribose) polymerase inhibitors on ischemia-reperfusion-induced myocardial injury Rupinder K. Sodhi ;Manjeet Singh ;Nirmal Singh ;Amteshwar S. Jaggi pp.1037-1043

Enhanced transfection of polyplexes based on pluronic-polypropylenimine dendrimer for gene transfer Junguo Hao ;Xianyi Sha ;Yuanjia Tang ;Ye Jiang ;Zhiwen Zhang ;Wei Zhang ;Yajuan Li ;Xiaoling Fang pp.1045-1054

Studies on the formation of hydrophobic ion-pairing complex of alendronate Sung-Kyun You ;Hae-Hyun Kwon ;Jeong-Min Lee ;Sang-Chul Shin ;Cheong-Weon Cho pp.1055-1060

Induction of quinone reductase activity by psoralidin isolated from Psoralea corylifolia in mouse Hepa 1c1c7 cells Sung-Jin Lee ;Kung-Woo Nam ;Woongchon Mar pp.1061-1065

Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate Srinivasan Shanmugam ;Chung-Kil Song ;Santhoshkumar Nagayya-Sriraman ;Rengarajan Baskaran ;Chul-Soon pp.1067-1075

Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-κB-inducing kinase-specific siRNA using liver-targeting liposomes Hyun-Ah Cho ;In-Sung Park ;Tae-Woo Kim ;Yu-Kyoung Oh ;Ki-Sook Yang ;Jin-Seok Kim pp.1077-1086

An investigation into effects of in vitro test condition on the release properties of theophylline from HPMC matrices using factorial design Aleksandra Petrovic ;Svetlana Ibric ;Svetlana Trajkovic ;Radmila Popovic ;Zorica Djuric ;Dragica Pop pp.1087-1096

참고문헌 (26건) : 자료제공( 네이버학술정보 )

참고문헌 목록에 대한 테이블로 번호, 참고문헌, 국회도서관 소장유무로 구성되어 있습니다.
번호 참고문헌 국회도서관 소장유무
1 Glutathione S-transferases: biomedical applications. 네이버 미소장
2 Valproic acid hepatic fatalities. III. U.S. experience since 1986. 네이버 미소장
3 Distribution and metabolism of intravenously injected tritiated insulin in rats 네이버 미소장
4 Dickinson, R. G., Hooper, W. D., Dunstan, P. R., and Eadic, M. J., Urinary excretion of valproate and some metabolites in chronically treated patients. Ther. Drug Monit., 11, 127-133 (1989). 미소장
5 Gopaul, S. V., Mutlib, A., and Farrell, K., Identification and characterization of N-acetylcystein conjugates of valproic acid in patients on valproic acid therapy. Drug Metab. Dispos., 28, 823-832 (2000). 미소장
6 The Hepatotoxicity of Valproic Acid and Its Metabolites in Rats. II. Intermediary and Valproic Acid Metabolism 네이버 미소장
7 Aspects of the metabolism of valproic acid. 네이버 미소장
8 Effects of sodium valproate on renal functions in rats. 네이버 미소장
9 Kassahun, K., Farrell, K., and Abbott, F. S., Identification and characterization of the glutathione and N-acetyl conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid in rats and humans. Drug Metab. Dispos., 19, 525-535 (1991). 미소장
10 Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid 네이버 미소장
11 Plasma α-Glutathione S- Transferase 네이버 미소장
12 Determination of plasma alpha-glutathione S-transferases in patients with HCV-related chronic infection: its significance and possible clinical relevance. 네이버 미소장
13 Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action 네이버 미소장
14 Abnormal metabolism of carnitine and valproate in a case of acute encephalopathy during chronic valproate therapy 네이버 미소장
15 Chromatographic Data (1980) 네이버 미소장
16 Pharmacological and Therapeutic Properties of Valproate 네이버 미소장
17 Effect of spinal anaesthesia on plasma concentrations of glutathione S‐transferase 네이버 미소장
18 Rettenmeier, A. W., Gordon, W. P., Prickett, K. S., Levy, R. H., and Baillie, T. A., Biotransformation and pharmacokinetic in the rhesus monkey of 2-n-propyl-4-pentanoic acid, a toxic metabolite of valproic acid. Drug Metab. Dispos. 14, 454-464 (1986). 미소장
19 Rettenmeier, A. W., Prickett, K. S., Gordon, W. P., Bjorge, S. M., Chang, S. L., Levy, R. H., and Baillie, T. A., Studies on the biotransformation in the perfused rat liver of 2-npropyl- 4-pentanoic acid, a metabolite of antiepileptic drug valproic acid. Drug Metab. Dispos., 13, 81-96 (1985). 미소장
20 Valproate (VPA) Metabolites in Various Clinical Conditions of Probable VPA-Associated Hepatotoxicity 네이버 미소장
21 Sugimoto, T., Nishida, N., Yasuhara, A., Ono, A., Sakane, Y., and Matsumura, T., Reye-like syndrome associated with valproic acid. Brain Dev., 5, 334-337 (1983). 미소장
22 Valproic Acid II: Effects on Oxidative Stress, Mitochondrial Membrane Potential, and Cytotoxicity in Glutathione-Depleted Rat Hepatocytes 네이버 미소장
23 Wang, P., Ba, Z. F., Tait, S. M., Zhou, M., Chaudry, I. H., Alterations in circulation blood volume during polymicrobial sepsis. Circ. Shock, 40, 92-98 (1993). 미소장
24 Yu, H. Y. and Shin, M. C., Determination of valproic acid in human plasma by capillary gas chromatography. Therp. Drug Monit., 18, 107-108 (1996). 미소장
25 Sodium Valproate in the Induction of Unusual Hepatotoxicity 네이버 미소장
26 Valproate-Induced Hepatic Injury: Analyses of 23 Fatal Cases 네이버 미소장

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